Diclofenac is a medicine that helps with pain and swelling in conditions like arthritis (a condition that causes pain, swelling, and stiffness in the joints, which are the places where two bones meet)) and gout (a type of arthritis). In 2013, the European Medicines Agency raised concerns about its safety. They took steps to reduce the risks, such as advising doctors when not to give diclofenac to patients, especially those with heart problems or a history of stroke. They also warned against its use in people with high blood pressure, high cholesterol, and diabetes (a disease where the body has trouble controlling blood sugar).
Researchers have studied how these safety steps have affected the general use of diclofenac, but it's not clear how they have impacted people who really need it for arthritis or muscle and joint problems. This project aims to find out how these safety measures have influenced the use of diclofenac and its alternatives in patients at higher risk of side effects, like those with heart disease, high blood pressure, high cholesterol, and diabetes. The goal is to see if these measures have changed the treatment choices and outcomes for these patients.
A population-based longitudinal observational study will be conducted using data from the CPRD database to examine anti-inflammatory drug prescription patterns and trends of health outcomes related to the use of diclofenac and its alternatives. The study population will consist of all patients registered with the CPRD database during the study period who will be followed up until death, end of follow-up or end of registration. The population of interest will be selected based on recorded diagnoses that are considered indications for diclofenac (arthritic conditions, acute musculo-skeletal disorders, or other painful conditions). The outcomes of interest will be changes in prescribing patterns of diclofenac and its alternatives. We will use interrupted time series regression to determine whether statistically significant changes in prescribing were associated with regulatory interventions. The outcomes will be assessed based on patients risk profile (no documented risk, documented risk factors such as high blood pressure, high cholesterol, and diabetes, or documented contraindications such as heart failure, heart disease, peripheral artery disease, or stroke history). The primary goal of the study is to assess the impact of risk minimisation measures (RMMs) targeting diclofenac, taking into account the possible unintended effects of RMMs on the use of diclofenac alternatives.
- The quarterly incidence of diclofenac and its alternatives. It will be estimated and defined as the number of incident users during the quarter of interest divided by the person-time in days of the whole database population during that quarter divided by the number of days in that quarter.
- Proportion of initiators of diclofenac and its alternatives in patients that meet selected indications for diclofenac prescription. It will be estimated by the number of diclofenac or its alternatives initiators in the quarter divided by the number of patients that meet indication for diclofenac during that quarter.
- The quarterly prevalence of diclofenac and its alternatives . It will be estimated and defined as the number of prevalent users during the quarter of interest divided by the person-time in days of the whole database population during that quarter divided by the number of days in that quarter.
- The quarterly discontinuation rates of diclofenac and its alternatives. It will be estimated as the number of patients with a prescription for diclofenac that did not receive a new prescription for diclofenac at least 90 days after the end of estimated exposure.
- Proportion of discontinuers of diclofenac and its alternatives in patients that meet selected indications for diclofenac prescription. It will be estimated by the number of diclofenac or its alternatives initiators in the quarter divided by the number of patients that meet indication for diclofenac during that quarter.
- The average dose and duration of diclofenac use trend during the study period.
- The average diclofenac dose and treatment duration before and after the intervention.
Helga Gardarsdottir - Chief Investigator - Utrecht University
Patrick Souverein - Corresponding Applicant - Utrecht University
Satu Johanna Siiskonen - Collaborator - Utrecht University
Tomas Lasys - Collaborator - Utrecht University
Yared Santa Ana Tellez - Collaborator - Utrecht University